Multi-stage or tandem mass spectrometry involves two or more stages of mass selection, separation and/or analysis, typically with ions being fragmented between these stages. For instance, a tandem quadrupole mass spectrometer generally consists of a first resolving quadrupole mass filter, followed by a collision cell, followed a second resolving quadrupole mass filter and an ion detector.
Selective Ion Monitoring (“SRM”) is a known tandem quadrupole mass spectrometry technique wherein the first quadrupole mass filter is initially set to only transmit parent or precursor ions having a single specific mass to charge ratio (“m/z”). These parent or precursor ions are then fragmented in the collision cell and the resulting fragment ions are directed towards the second resolving quadrupole mass filter which is set to transmit only fragment ions having a specific mass to charge ratio towards the ion detector. Each SRM transition thus comprises a precursor-fragment ion pair. Multiple Reaction Monitoring (“MRM”) typically involves measuring multiple different precursor-fragment ion transitions.
The length of time that the ion current for a single acquisition (e.g. a particular MRM transition) is measured is known as the “dwell time”. The time between adjacent dwell times is known as the “interscan” or “interchannel” time. The “cycle time” is the sum of all of the dwell times and interscan times constituting the cycle.
In a MRM experiment, once a first transition has been measured, the instrument must then be reconfigured in order to measure a second different transition. It is also necessary to ensure that, following any reconfiguration, the ion current of the second transition is sufficiently stabilised to allow an accurate measurement to be made. This must be done before the second transition is measured and so these factors determine the length of the interscan time.
Known approaches for reducing the interscan time involve controlling the interscan time or the order at which transitions are measured based on the mass difference or difference in parameters between adjacent scans. However, these approaches are inherently of a serial nature. These techniques are fundamentally limited as the interscan time cannot be reduced below the transit time of ions through the mass spectrometer.
U.S. Pat. No. 7,638,762 (Russ) discloses a method of optimising the performance of a mass spectrometer when multiple measurements are made.
U.S. Pat. No. 8,410,436 (Mukaibatake) discloses a quadrupole mass spectrometer wherein a relatively short settling time is set.
U.S. Pat. No. 8,368,010 (Kawana) discloses a quadrupole mass spectrometer which is capable of reducing a settling time-period.
U.S. Pat. No. 8,084,733 (Russ) discloses a method for optimising the performance of a mass spectrometer.
US 2011/0006203 (Fujita) discloses a method of removing ions from a collision cell during a halt period when the introduction of ions is temporally discontinued to change the objective ion being monitored. Introduction of the second group of ions to the collision cell is only initiated after the introduction of a first group is discontinued.
US 2011/0248160 (Belov), US 2009/0057553 (Goodenowe), US 2012/0160998 (Kou) and US 2011/0315868 (Hirabayashi) disclose various methods utilizing ion traps or pulsed ion injection.
In Belav, a pulsed multiple reaction monitoring process is disclosed where the acquisition in the Q3 quadrupole is changed in synchronisation with the release of ions from an upstream ion trap. The ions for the second reaction are therefore only transmitted after Q3 is reconfigured.
WO 2013/092923 (Makarov) discloses a mass spectrometer containing parallel collision cells to which precursor ions may sequentially be directed.
WO 2012/143728 (Green) discloses a method of fast switching. The instrument is intentionally not allowed to equilibrate after switching so no interscan time can be defined.
EP-2642509 (Hitachi) discloses a method of adjusting an accelerating voltage applied across a collision chamber based on mass to charge ratio so that all fragment ions have the same velocity.
Several of the known arrangements require relatively complicated instrument geometries or control systems.
It is desired to reduce the interscan time between successive MRM transitions.